First in Human Study of the Infusion of ARI0003 Cells in Relapsed/Refractory to Treatment B-cell Aggressive Lymphoma

NCT06097455 | Not Yet Recruiting Early Phase 1 DMC

• 2 other identifiers: CARTD-BG-12023-5072-13-97-00
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

ths study consist in testing a CAR T therapy (ARI0003 cells (antiCD19 and antiBCMA) in patients suffering relapsed NHL (that means that symptoms of NHL reappeared ) or refractory (that means that they did not respond to other treatments). This is a first in human study.

Conditions

Refractory Non-Hodgkin Lymphoma; Relapsed Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Rate of > grade 3 CRS and/or ICANS

  Rate of patients who develop grade \> 3 cytokine release syndrome (CRS) and/or grade \> 3 immune cell associated neurotoxicity syndrome (ICANS) according to the criteria and grading defined in the international consensus document of the American Society for Transplantation and Cellular Therapy (ASTCT criteria). ASTCT score can be between 1 and 4 (being 1 the minimum value and 4 the maximum) and where higher score means worse outcome.

  in the first 30 days after ARI0003 administration

• ORR

  Overall response rate (ORR) according to Lugano criteria (best response within 3 months post ARI0003 infusion

  within 3 months post ARI0003 infusion

Secondary Outcomes (6)

• Procedure-related mortality (PRM)

  through study completion, an average of 24 months

• Toxicity: incidence of AE

  at 3 and 12 months

• Complete response rate

  at 3 months

• Duration of response,

  from month 3 to study completion, an average of 24 months

• Progression-free survival

  through study completion, an average of 24 months

Study Arms (1)

ARI0003

EXPERIMENTAL

ARI0003 will be administered intravenously under a split regime. A total dose between 0.5 and 5 x106 cell/Kg will be administered in 3 administrations (fractions):

Genetic: ARI0003

Interventions

ARI0003 GENETIC

Treatment with ARI0003 cells

Also known as: Adult autologous differentiated T-cells from peripheral blood, expanded and co-transduced lentiviruses: one containing a chimeric antigen receptor anti-CD19 and another containing an anti-CD269 (BCMA)

ARI0003

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Diagnosis of CD19+ or CD269+ relapsed/refractory (R/R) aggressive B-cell lymphoma in one of the following circumstances:
• Burkitt's lymphoma;
• Histology not covered by approved CART19-cell products (plasmablastic lymphoma, primary effusion lymphoma, intravascular lymphoma, transformed lymphoma from marginal zone lymphoma or chronic lymphocytic leukaemia, primary cutaneous DLBCL, T-cell rich DLBCL, high-grade B-cell lymphoma, grey zone lymphoma or grade 3b follicular lymphoma); or
• Aggressive B-cell lymphoma that is refractory or relapsing after treatment with CART19-cell therapy.

You may not qualify if:

• \. Any experimental or non-commercialized therapy in the previous 4 weeks. 2. Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer, except for non-melanoma skin cancer or completely resected in situ carcinoma.
• \. Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent).
• \. Active infection requiring systemic medical therapy. 5. Active HBV or HCV infection. 6. Positive serology for HIV. 7. Any concomitant and uncontrolled medical disease. 8. Severe organic impairment defined by cardiac ejection fraction \<40%, DLCO \<40%, GFR \<30 ml/min or bilirubin \>3 times the upper limit of normality (unless due to Gilbert's syndrome).
• \. Lactating or pregnant women. 10. Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures from the beginning until the end of the study.
• \. CNS disease in the form of a macroscopic solid lesion in the encephalon or spinal cord (isolated meningeal disease is allowed

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

Study Sites (7)

CHU Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Location

Hospital Clínic Barcelona

Barcelona, 08036, Spain

Location

H. Ramon y Cajal

Madrid, Spain

Location

H.U. Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Central de Asturias

Oviedo, Spain

Location

Hospital Son Espases

Palma de Mallorca, Spain

Location

H. Clínico de Salamanca

Salamanca, Spain

Location

Related Publications (1)

• Bachiller M, Barcelo-Genestar N, Rodriguez-Garcia A, Alserawan L, Dobano-Lopez C, Gimenez-Alejandre M, Castellsague J, Colell S, Otero-Mateo M, Antonana-Vildosola A, Espanol-Rego M, Ferruz N, Pascal M, Martin-Antonio B, Anguela XM, Fillat C, Olesti E, Calvo G, Juan M, Delgado J, Perez-Galan P, Urbano-Ispizua A, Guedan S. ARI0003: Co-transduced CD19/BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma. Mol Ther. 2025 Jan 8;33(1):317-335. doi: 10.1016/j.ymthe.2024.11.028. Epub 2024 Nov 19.

  PMID: 39563035 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Julio Delgado, MD PhD

CONTACT

+34932275400; jdelgado@clinic.cat

Sara Varea, MSc

CONTACT

+34932275400; svarea@clinic.cat

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2023
• First Posted: October 24, 2023
• Study Start: January 15, 2024
• Primary Completion: April 15, 2025
• Study Completion (Estimated): January 15, 2027
• Last Updated: October 26, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7)